Case report: atypical presentation of acute disseminated encephalomyelitis after tick-borne encephalitis.

Acute disseminated encephalomyelitis (ADEM) is a rare and an immune- mediated inflammatory illness of the central nervous system that normally demonstrates as a monophasic disorder connected with multifocal neurologic symptoms. Herein, we report atypical presentation of ADEM presenting as single lesions in a middle-aged woman after tick-borne encephalitis.

Mutations in EPHB4 cause human venous valve aplasia.

Venous valve (VV) failure causes chronic venous insufficiency, but the molecular regulation of valve development is poorly understood. A primary lymphatic anomaly, caused by mutations in the receptor tyrosine kinase EPHB4, was recently described, with these patients also presenting with venous insufficiency. Whether the venous anomalies are the result of an effect on VVs is not known. VV formation requires complex "organization" of valve-forming endothelial cells, including their reorientation perpendicular to the direction of blood flow. Using quantitative ultrasound, we identified substantial VV aplasia and deep venous reflux in patients with mutations in EPHB4. We used a GFP reporter in mice to study expression of its ligand, ephrinB2, and analyzed developmental phenotypes after conditional deletion of floxed Ephb4 and Efnb2 alleles. EphB4 and ephrinB2 expression patterns were dynamically regulated around organizing valve-forming cells. Efnb2 deletion disrupted the normal endothelial expression patterns of the gap junction proteins connexin37 and connexin43 (both required for normal valve development) around reorientating valve-forming cells and produced deficient valve-forming cell elongation, reorientation, polarity, and proliferation. Ephb4 was also required for valve-forming cell organization and subsequent growth of the valve leaflets. These results uncover a potentially novel cause of primary human VV aplasia.

Human venous valve disease caused by mutations in FOXC2 and GJC2.

Venous valves (VVs) prevent venous hypertension and ulceration. We report that FOXC2 and GJC2 mutations are associated with reduced VV number and length. In mice, early VV formation is marked by elongation and reorientation ("organization") of Prox1hi endothelial cells by postnatal day 0. The expression of the transcription factors Foxc2 and Nfatc1 and the gap junction proteins Gjc2, Gja1, and Gja4 were temporospatially regulated during this process. Foxc2 and Nfatc1 were coexpressed at P0, and combined Foxc2 deletion with calcineurin-Nfat inhibition disrupted early Prox1hi endothelial organization, suggesting cooperative Foxc2-Nfatc1 patterning of these events. Genetic deletion of Gjc2, Gja4, or Gja1 also disrupted early VV Prox1hi endothelial organization at postnatal day 0, and this likely underlies the VV defects seen in patients with GJC2 mutations. Knockout of Gja4 or Gjc2 resulted in reduced proliferation of Prox1hi valve-forming cells. At later stages of blood flow, Foxc2 and calcineurin-Nfat signaling are each required for growth of the valve leaflets, whereas Foxc2 is not required for VV maintenance.

A dedicated vascular access clinic for children on haemodialysis: Two years' experience.

BACKGROUND: Arteriovenous fistula (AVF) formation for long-term haemodialysis in children is a niche discipline with little data for guidance. We developed a dedicated Vascular Access Clinic that is run jointly by a transplant surgeon, paediatric nephrologist, dialysis nurse and a clinical vascular scientist specialised in vascular sonography for the assessment and surveillance of AVFs. We report the experience and 2-year outcomes of this clinic. METHODS: Twelve new AVFs were formed and 11 existing AVFs were followed up for 2 years. All children were assessed by clinical and ultrasound examination. RESULTS: During the study period 12 brachiocephalic, nine basilic vein transpositions and two radiocephalic AVFs were followed up. The median age (interquartile range) and weight of those children undergoing new AVF creation were 9.4 (interquartile 3-17) years and 26.9 (14-67) kg, respectively. Pre-operative ultrasound vascular mapping showed maximum median vein and artery diameters of 3.0 (2-5) and 2.7 (2.0-5.3) mm, respectively. Maturation scans 6 weeks after AVF formation showed a median flow of 1277 (432-2880) ml/min. Primary maturation rate was 83 % (10/12). Assisted maturation was 100 %, with two patients requiring a single angioplasty. For the 11 children with an existing AVF the maximum median vein diameter was 14.0 (8.0-26.0) mm, and the median flow rate was 1781 (800-2971) ml/min at a median of 153 weeks after AVF formation. Twenty-two AVFs were used successfully for dialysis, a median kt/V of 1.97 (1.8-2.9), and urea reduction ratio of 80.7 % (79.3-86 %) was observed. One child was transplanted before the AVF was used. CONCLUSIONS: A multidisciplinary vascular clinic incorporating ultrasound assessment is key to maintaining young children on chronic haemodialysis via an AVF.